Molecular mechanisms of fat deposition: <i>IL-6</i> is a hub gene in fat lipolysis, comparing thin-tailed with fat-tailed sheep breeds

Abstract

Abstract. Tail fat content affects meat quality and varies significantly among different breeds of sheep. Ghezel (fat-tailed) and Zel (thin-tailed) are two important Iranian local sheep breeds with different patterns of fat storage. The current study presents the transcriptome characterization of tail fat using RNA sequencing in order to get a better comprehension of the molecular mechanism of lipid storage in the two mentioned sheep breeds. Seven (Zel = 4 and Ghezel = 3) 7-month-old male lambs were used for this experiment. The results of sequencing were analyzed with bioinformatics methods, including differentially expressed genes (DEGs) identification, functional enrichment analysis, structural classification of proteins, protein–protein interaction (PPI) and network and module analyses. Some of the DEGs, such as LIPG, SAA1, SOCS3, HIF-1α, and especially IL-6, had a close association with lipid metabolism. Furthermore, functional enrichment analysis revealed pathways associated with fat deposition, including “fatty acid metabolism”, “fatty acid biosynthesis” and “HIF-1 signaling pathway”. The structural classification of proteins showed that major down-regulated DEGs in the Zel (thin-tailed) breed were classified under transporter class and that most of them belonged to the solute carrier transporter (SLC) families. In addition, DEGs under the transcription factor class with an important role in lipolysis were up-regulated in the Zel (thin-tailed) breed. Also, network analysis revealed that IL-6 and JUNB were hub genes for up-regulated PPI networks, and HMGCS1, VPS35 and VPS26A were hub genes for down-regulated PPI networks. Among the up-regulated DEGs, the IL-6 gene seems to play an important role in lipolysis of tail fat in thin-tailed sheep breeds via various pathways such as tumor necrosis factor (TNF) signaling and mitogen-activated protein kinase (MAPK) signaling pathways. Due to the probable role of the IL-6 gene in fat lipolysis and also due to the strong interaction of IL-6 with the other up-regulated DEGs, it seems that IL-6 accelerates the degradation of lipids in tail fat cells.

Deciphering the role of alternative splicing as a potential regulator in fat-tail development of sheep: a comprehensive RNA-seq based study

“…First, to compare the identified DAS genes with the reported DEGs in the previous cohort studies, a comprehensive literature review was performed. It is of interest to note that 50 DAS genes were reported as DEGs in these studies 6 , 7 , 9 – 11 , 16 . These genes are listed in Supplementary File S5 .…”

“…Recent studies have shown that AS is more frequent and complex than initially thought, and AS is likely to be involved in shaping the variations among species and breeds. Previous studies have mainly focused on the transcriptional level to explore the genetic mechanisms behind the fat-tail formation in sheep 6 , 7 , 9 – 11 , 16 , leaving the other important post-transcriptional regulation mechanisms, such as AS, that may also contribute to the evolution of biological complexity and phenotypic diversity in sheep fat-tail. Here, taking advantage of RNA-Seq method, a large number of samples related to seven studies, with the same purpose, were applied to elucidate the potential roles of AS regulation in forming the fat-tail of sheep.…”

“…These reports have resulted in a growing interest in understanding of AS events in various biological process as well as among different breeds. Although several studies have investigated the transcriptome differences between fat- and thin-tailed sheep breeds 6 , 7 , 9 – 11 , 16 , comprehensive alterations of AS and their biological implications in fat deposition in tail of sheep has not been elucidated, yet. Fortunately, a large number of public RNA-Seq datasets provide an opportunity to investigate role of AS in gene regulation in fat-tail formation of sheep, which can be overlooked in standard transcriptome analysis.…”

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

“…This observation prompted us to investigate further by differentiating these cells into adipocytes. Intriguingly, in fructose-treated mouse fibroblasts, there was a remarkable increase in IL6, a well-known cytokine that stimulates lipolysis 58–60 . This was supported by the significant upregulation of Hsl concomitant with the increase in Cpt1 expression.…”

Genetics of the phenotypic evolution in sheep: a molecular look at diversity-driving genes

“…Table S2. Sheep tails from a transcriptomic perspective: mRNA profiles [4,12,14,20,21,219,[227][228][229][230][231][232][233][234][235][236][237][238][239][240][241]. Table S3.…”